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Treatment of experimental autoimmune uveoretinitis with peroxisome proliferator-activated receptor α agonist fenofibrate.

Osada M, Sakai T, Kuroyanagi K, Kohno H, Tsuneoka H - Mol. Vis. (2014)

Bottom Line: DTH was significantly inhibited in the fenofibrate-treated groups, compared with the vehicle-treated groups (controls).Lymphocyte proliferation assay demonstrated decreased proliferation in the presence of 25 mg/ml S-Ag peptide in the fenofibrate-treated groups compared with controls.The current results indicate that fenofibrate administered orally following clinical onset has therapeutic effect in EAU.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan.

ABSTRACT

Purpose: The peroxisome proliferator-activated receptor α (PPARα) agonist has been approved for treating hypercholesterolemia and lipid abnormalities. Researchers have recently discovered that an anti-inflammatory effect of PPAR agonist may have the potential to treat autoimmune disease. This study aims to investigate the therapeutic effects of fenofibrate on experimental autoimmune uveoretinitis (EAU).

Methods: EAU was induced in Lewis rats using bovine S-antigen (S-Ag) peptide. Fenofibrate was suspended in 3% arabic gum and administered orally at a high dose of 100 mg/kg and at a low dose of 20 mg/kg every day. Fenofibrate treatment was initiated after the clinical onset once daily for 14 days. The rats were examined every other day for clinical signs of EAU. The histological scores and delayed-type hypersensitivity (DTH) were evaluated on day 28 post-immunization. Morphologic and immunohistochemical examinations were performed with light and confocal microscopy, respectively. Lymphocyte proliferation was measured with [3H] thymidine incorporation into antigen-stimulated T cells from inguinal lymph nodes.

Results: Clinical and histological scores of EAU were decreased in the fenofibrate-treated groups. The expression of inflammatory cytokines and Müller cell proliferation were inhibited in the fenofibrate-treated groups. DTH was significantly inhibited in the fenofibrate-treated groups, compared with the vehicle-treated groups (controls). Lymphocyte proliferation assay demonstrated decreased proliferation in the presence of 25 mg/ml S-Ag peptide in the fenofibrate-treated groups compared with controls.

Conclusions: The current results indicate that fenofibrate administered orally following clinical onset has therapeutic effect in EAU. Fenofibrate may be useful for treating intraocular inflammation.

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Related in: MedlinePlus

Immunohistochemistry of the retina of rats with experimental autoimmune uveoretinitis. Representative results for expression of vascular endothelial growth factor (VEGF; green) and glutamine synthetase (GS; red) are shown on day 28 post-immunization treated with vehicle (A), low-dose fenofibrate (FF(20); B), and high-dose fenofibrate (FF(100); C). Increased expression of VEGF was observed in Müller cells (A and B). Rats treated with high-dose fenofibrate showed faint expression of VEGF in Müller cells and a marked decrease in ocular infiltrative cells (C). The bar represents 50 µm.
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f4: Immunohistochemistry of the retina of rats with experimental autoimmune uveoretinitis. Representative results for expression of vascular endothelial growth factor (VEGF; green) and glutamine synthetase (GS; red) are shown on day 28 post-immunization treated with vehicle (A), low-dose fenofibrate (FF(20); B), and high-dose fenofibrate (FF(100); C). Increased expression of VEGF was observed in Müller cells (A and B). Rats treated with high-dose fenofibrate showed faint expression of VEGF in Müller cells and a marked decrease in ocular infiltrative cells (C). The bar represents 50 µm.

Mentions: Immunohistochemical results for retinas collected on day 28 post-immunization from rats treated with vehicle and fenofibrate are shown in Figure 4. In the vehicle- or low-dose fenofibrate-treated retinas, GS (red) and VEGF (green) were expressed in activated Müller cells (Figure 4A,B). Rats treated with high-dose fenofibrate (100 mg/kg) showed less VEGF expression (Figure 4C).


Treatment of experimental autoimmune uveoretinitis with peroxisome proliferator-activated receptor α agonist fenofibrate.

Osada M, Sakai T, Kuroyanagi K, Kohno H, Tsuneoka H - Mol. Vis. (2014)

Immunohistochemistry of the retina of rats with experimental autoimmune uveoretinitis. Representative results for expression of vascular endothelial growth factor (VEGF; green) and glutamine synthetase (GS; red) are shown on day 28 post-immunization treated with vehicle (A), low-dose fenofibrate (FF(20); B), and high-dose fenofibrate (FF(100); C). Increased expression of VEGF was observed in Müller cells (A and B). Rats treated with high-dose fenofibrate showed faint expression of VEGF in Müller cells and a marked decrease in ocular infiltrative cells (C). The bar represents 50 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4225135&req=5

f4: Immunohistochemistry of the retina of rats with experimental autoimmune uveoretinitis. Representative results for expression of vascular endothelial growth factor (VEGF; green) and glutamine synthetase (GS; red) are shown on day 28 post-immunization treated with vehicle (A), low-dose fenofibrate (FF(20); B), and high-dose fenofibrate (FF(100); C). Increased expression of VEGF was observed in Müller cells (A and B). Rats treated with high-dose fenofibrate showed faint expression of VEGF in Müller cells and a marked decrease in ocular infiltrative cells (C). The bar represents 50 µm.
Mentions: Immunohistochemical results for retinas collected on day 28 post-immunization from rats treated with vehicle and fenofibrate are shown in Figure 4. In the vehicle- or low-dose fenofibrate-treated retinas, GS (red) and VEGF (green) were expressed in activated Müller cells (Figure 4A,B). Rats treated with high-dose fenofibrate (100 mg/kg) showed less VEGF expression (Figure 4C).

Bottom Line: DTH was significantly inhibited in the fenofibrate-treated groups, compared with the vehicle-treated groups (controls).Lymphocyte proliferation assay demonstrated decreased proliferation in the presence of 25 mg/ml S-Ag peptide in the fenofibrate-treated groups compared with controls.The current results indicate that fenofibrate administered orally following clinical onset has therapeutic effect in EAU.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan.

ABSTRACT

Purpose: The peroxisome proliferator-activated receptor α (PPARα) agonist has been approved for treating hypercholesterolemia and lipid abnormalities. Researchers have recently discovered that an anti-inflammatory effect of PPAR agonist may have the potential to treat autoimmune disease. This study aims to investigate the therapeutic effects of fenofibrate on experimental autoimmune uveoretinitis (EAU).

Methods: EAU was induced in Lewis rats using bovine S-antigen (S-Ag) peptide. Fenofibrate was suspended in 3% arabic gum and administered orally at a high dose of 100 mg/kg and at a low dose of 20 mg/kg every day. Fenofibrate treatment was initiated after the clinical onset once daily for 14 days. The rats were examined every other day for clinical signs of EAU. The histological scores and delayed-type hypersensitivity (DTH) were evaluated on day 28 post-immunization. Morphologic and immunohistochemical examinations were performed with light and confocal microscopy, respectively. Lymphocyte proliferation was measured with [3H] thymidine incorporation into antigen-stimulated T cells from inguinal lymph nodes.

Results: Clinical and histological scores of EAU were decreased in the fenofibrate-treated groups. The expression of inflammatory cytokines and Müller cell proliferation were inhibited in the fenofibrate-treated groups. DTH was significantly inhibited in the fenofibrate-treated groups, compared with the vehicle-treated groups (controls). Lymphocyte proliferation assay demonstrated decreased proliferation in the presence of 25 mg/ml S-Ag peptide in the fenofibrate-treated groups compared with controls.

Conclusions: The current results indicate that fenofibrate administered orally following clinical onset has therapeutic effect in EAU. Fenofibrate may be useful for treating intraocular inflammation.

Show MeSH
Related in: MedlinePlus